Atheroarteriosclerosis, closely resembling that in man, was induced by clone-purified cell-free Marek's disease herpesvirus (MDV) in normocholesterolemic and hypercholesterolemic specific pathogen free (SPF) chickens. Gross arterial lesions have been observed beginning approximately three months post inoculation in a current pathogenesis experiment. Persistent widespread human infections with up to five herpesviruses suggest that our findings may be significant in understanding the etiology and pathogenesis of human arteriosclerosis. The proposed experiments are designed to extend our knowledge of the mechanisms involved in viral-induced atheroarteriosclerosis by characterization of virus-host interactions and histopathogenesis of the arterial lesions. The early and evolving lesions will be characterized by fluorescence microscopy, paraffin histology and electron microscopy. Similar techniques will be employed for detecting the presence of herpesviruses in normal and atherosclerotic human arterial specimens. Vascular smooth muscle cell cultures derived from SPF chickens were infected with MDV. A marked increase in oil red O stained lipid was observed in virus infected as compared to parallel uninfected cell cultures. Lipid analyses (cholesterol, triglycerides, etc.) will be compared in similar infected and control cultures. This will determine whether alterations of cellular lipid metabolism are caused by herpesvirus infection.